Cabergoline Decreases Alcohol Drinking and Seeking Behaviors Via Glial Cell Line-Derived Neurotrophic Factor

Background: Cabergoline is an ergotamine derivative that increases the expression of glial cell line-derived neurotrophic factor (GDNF) in vitro. We recently showed that GDNF in the ventral tegmental area (VTA) reduces the motivation to consume alcohol. We therefore set out to determine whether cabergoline administration decreases alcohol-drinking and -seeking behaviors via GDNF. Methods: Reverse transcription polymerase chain reaction (RT-PCR) and Enzyme-Linked ImmunoSorbent Assay (ELISA) were used to measure GDNF levels. Western blot analysis was used for phosphorylation experiments. Operant self-administration in rats and a two-bottle choice procedure in mice were used to assess alcohol-drinking behaviors. Instrumental performance tested during extinction was used to measure alcohol-seeking behavior. The [35S]GTPγS binding assay was used to assess the expression and function of the dopamine D2 receptor (D2R). Results: We found that treatment of the dopaminergic-like cell line SH-SY5Y with cabergoline and systemic administration of cabergoline in rats resulted in an increase in GDNF level and in the activation of the GDNF pathway. Cabergoline treatment decreased alcohol-drinking and -seeking behaviors including relapse, and its action to reduce alcohol consumption was localized to the VTA. Finally, the increase in GDNF expression and the decrease in alcohol consumption by cabergoline were abolished in GDNF heterozygous knockout mice. Conclusions: Together, these findings suggest that cabergoline-mediated upregulation of the GDNF pathway attenuates alcohol-drinking behaviors and relapse. Alcohol abuse and addiction are devastating and costly problems worldwide. This study puts forward the possibility that cabergoline might be an effective treatment for these disorders. © 2009 Society of Biological Psychiatry.

Case management in action: An examination of two cases in the area of alcohol related brain damage

‘Practice Forum’ provides a forum for social work practitioners to share their practice with others; to describe what they are doing and assess its effectiveness. The practice of case management is applied in a wide range of service delivery models to meet complex client needs. Unfortunately, cost containment and lack of clarity of the role of the case manager has blurred the definition and practice of case management for both the consumer and professional providers. This article examines two cases of a small non-government agency in Melbourne called Alcohol Related Brain Injury Assessment, Accommodation & Support Inc. (ARBIAS) where case management services are delivered to people with alcohol acquired brain damage. The analysis presented here supports the view that continuity of care and intensive relationship building with clients is vital for successful client outcomes and has application to a variety of programs which service chronically disabled clients.

Cognitive Functioning in Alcohol and Other Substance Use Disorders in Young Adulthood : A Genetic Epidemiological Study

Alcohol and other substance use disorders (SUDs) result in great costs and suffering for individuals and families and constitute a notable public health burden. A multitude of factors, ranging from biological to societal, are associated with elevated risk of SUDs, but at the level of individuals, one of the best predictors is a family history of SUDs. Genetically informative twin and family studies have consistently indicated this familial risk to be mainly genetic. In addition, behavioral and temperamental factors such as early initiation of substance use and aggressiveness are associated with the development of SUDs. These familial, behavioral and temperamental risk factors often co-occur, but their relative importance is not well known. People with SUDs have also been found to differ from healthy controls in various domains of cognitive functioning, with poorer verbal ability being among the most consistent findings. However, representative population-based samples have rarely been used in neuropsychological studies of SUDs. In addition, both SUDs and cognitive abilities are influenced by genetic factors, but whether the co-variation of these traits might be partly explained by overlapping genetic influences has not been studied. Problematic substance use also often co-occurs with low educational level, but it is not known whether these outcomes share part of their underlying genetic influences. In addition, educational level may moderate the genetic etiology of alcohol problems, but gene-environment interactions between these phenomena have also not been widely studied. The incidence of SUDs peaks in young adulthood rendering epidemiological studies in this age group informative. This thesis investigated cognitive functioning and other correlates of SUDs in young adulthood in two representative population-based samples of young Finnish adults, one of which consisted of monozygotic and dizygotic twin pairs enabling genetically informative analyses. Using data from the population-based Mental Health in Early Adulthood in Finland (MEAF) study (n=605), the lifetime prevalence of DSM-IV any substance dependence or abuse among persons aged 21—35 years was found to be approximately 14%, with a majority of the diagnoses being alcohol use disorders. Several correlates representing the domains of behavioral and affective factors, parental factors, early initiation of substance use, and educational factors were individually associated with SUDs. The associations between behavioral and affective factors (attention or behavior problems at school, aggression, anxiousness) and SUDs were found to be largely independent of factors from other domains, whereas daily smoking and low education were still associated with SUDs after adjustment for behavioral and affective factors. Using a wide array of neuropsychological tests in the MEAF sample and in a subsample (n=602) of the population-based FinnTwin16 (FT16) study, consistent evidence of poorer verbal cognitive ability related to SUDs was found. In addition, participants with SUDs performed worse than those without disorders in a task assessing psychomotor processing speed in the MEAF sample, whereas no evidence of more specific cognitive deficits was found in either sample. Biometrical structural equation models of the twin data suggested that both alcohol problems and verbal ability had moderate heritabilities (0.54—0.72), and that their covariation could be explained by correlated genetic influences (genetic correlations -0.20 to -0.31). The relationship between educational level and alcohol problems, studied in the full epidemiological FT16 sample (n=4,858), was found to reflect both genetic correlation and gene-environment interaction. The co-occurrence of low education and alcohol problems was influenced by overlapping genetic factors. In addition, higher educational level was associated with increased relative importance of genetic influences on alcohol problems, whereas environmental influences played a more important role in young adults with lower education. In conclusion, SUDs, especially alcohol abuse and dependence, are common among young Finnish adults. Behavioral and affective factors are robustly related to SUDs independently of many other factors, and compared to healthy peers, young adults who have had SUDs during their life exhibit significantly poorer verbal cognitive ability, and possibly less efficient psychomotor processing. Genetic differences between individuals explain a notable proportion of individual differences in risk of alcohol dependence, verbal ability, and educational level, and the co-occurrence of alcohol problems with poorer verbal cognition and low education is influenced by shared genetic backgrounds. Finally, various environmental factors related to educational level in young adulthood moderate the relative importance of genetic factors influencing the risk of alcohol problems, possibly reflecting differences in social control mechanisms related to educational level.

Patrons de consum d'alcohol en estudiants universitaris

L’objectiu general d’aquesta tesi és conèixer la prevalença i el patró de consum d’alcohol d’una mostra de 2,137 estudiants de la Universitat de Girona (17-35 anys). S’utilitzà un disseny multimètode integrant la metodologia quantitativa (estudi d’enquesta) amb la metodología qualitativa (grups focals). Un 65% dels joves són consumidors habituals d’alcohol. La influència social de pares, germans i amics és una variable crucial en la iniciació i manteniment del consum d’aquesta droga. El consum habitual és més freqüent entre aquells que van experimentar més precoçment amb la substància. Entre els homes és més habitual el consum massiu, però més dones efectuen consums considerats d’alt risc. Els joves reconeixen algunes repercussions socials de l’abús de l’alcohol però no en perceben per a la salut física. Aquests resultats mostren la necessitat de: endarrerir l’edat de primera experimentació, informar del risc del consum d’alcohol i fomentar un oci nocturn alternatiu i saludable.

Does the tendency to act impulsively underlie binge eating and alcohol use problems? An empirical investigation

The co-occurrence of problem drinking and binge eating and purging has been well documented. However, there has been relatively little investigation of etiological models that may influence the development of this  co-occurrence. This study tests the hypotheses that impulsivity is heightened in eating disordered women compared with controls, and that women with comorbid bulimia and alcohol use disorders show higher impulsivity than bulimic-only women. The Impulsivity scale, BIS/BAS scales, State Anxiety Inventory, and a behavioural measure of reward responsiveness (CARROT) were administered to 22 women with bulimia, 23 women with comorbid bulimia and alcohol abuse/dependence, and 21 control women. As hypothesised, eating disordered women scored higher than controls on several self-report measures of impulsivity and sorted cards faster during a financially rewarded trial on the behavioural task. Also, as predicted, comorbid women scored higher than bulimic women on the Impulsivity scale. These findings suggest that individual differences in impulsiveness and a tendency to approach rewarding stimuli may contribute to developing these disorders.

Prediction of alcohol-related harm from controlled drinking stragegies and alcohol consumption trajectories

Aims To establish predictors of age 21 alcohol-related harm from prior drinking patterns, current levels of alcohol consumption and use of controlled drinking strategies.
Participants One thousand, five hundred and ninety-six students recruited from an initial sample of 3300 during their final year of high school in 1993.
Design Longitudinal follow-up across five waves of data collection.
Setting Post high school in Victoria, Australia.
Measurements Self-administered surveys examining a range of health behaviours, including alcohol consumption patterns and related behaviour.
Findings Drinking behaviours at age 21 were found to be strongly predicted by drinking trajectories established through the transition from high school. Multivariate regression analysis revealed that alcohol-related harms at age 21 were reduced where current levels of alcohol use fell within limits recommended in Australian national guidelines. After controlling for this effect it was found that the range of strategies employed by participants to control alcohol use maintained a small protective influence. Post-high-school drinking trajectories continued to demonstrate a significant effect after controlling for current behaviours. Findings revealed that over one quarter of males and females drank alcohol, but on a less-than-weekly basis. This pattern of alcohol use demonstrated considerable stability through the post-school transition and was associated with a low level of subsequent harm at age 21.
Conclusions Future research should investigate whether encouraging more Australian adolescents to drink alcohol on a less-than-weekly basis may be a practical intervention target for reducing alcohol-related harms.

Youth alcohol and other drug use in the United States and Australia: a cross-national comparison of three state-wide samples

Although youth drug and alcohol harm minimization policies in Australia are often contrasted with the abstinence and zero tolerance policies adopted in the United States, there has been little research directly comparing youth substance use behaviour in the two countries. Three state representative samples in Victoria, Australia (n = 7898) and in the US states of Oregon (n = 15 224) and Maine (n = 16 245) completed a common cross-sectional student survey. Rates of alcohol use (lifetime alcohol use, recent use in the past 30 days), alcohol use exceeding recommended consumption limits (binge drinking: five or more drinks in a session), other licit drug use (tobacco use), and norm-violating substance use (substance use at school, use in the past 30 days of marijuana or other illicit drug use) were compared for males and females at ages 12-17. Rates were lower (odds ratios 0.5-0.8) for youth in Maine and Oregon compared to Victoria for lifetime and recent alcohol use, binge drinking and daily cigarette smoking. However, rates of recent marijuana use and recent use of other illicit drugs were higher in Maine and Oregon, as were reports of being drunk or high at school. In contradiction of harm minimization objectives, Victoria, relative to the US states of Oregon and Maine, demonstrated higher rates of alcohol use exceeding recommended consumption limits and daily tobacco use. However, findings suggested that aspects of norm-violating substance use (substance use at school, marijuana use and other illicit drug use) were higher in the US states compared to Victoria.

Adolescent alcohol-use trajectories in the transition from high school

A cohort of 3300 students from high schools across Victoria, Australia, were surveyed regarding their patterns of alcohol consumption from mid-1993 to 1995. The first wave of data was collected halfway through the students' final year of school (year 12). Students were then resurveyed 3 months following school completion and on two subsequent occasions, each separated by 6-month intervals. Analysis of the four waves of data indicated that five longitudinal patterns (trajectories) characterized temporal trends in male and female alcohol use through the transition from high school. Stable non-use trajectories were evident for 17% of males and 16% of females. Trajectories of less than weekly use characterized 45% of females and 46% of males, and showed little tendency to escalate toward harmful use. Among those using alcohol on a weekly or more frequent basis in high school, with few exceptions, use continued with at least the same frequency, but the quantity of alcohol consumed tended to escalate over time toward harmful levels. Overall, findings indicate that patterns of alcohol use tend to be stable over time, and more frequent alcohol use during the final year of high school tends to precede potentially harmful alcohol use following high school. Encouraging those high school students who consume alcohol once per week or more often to use alcohol on a less than weekly basis may be a valuable yet neglected harm minimization strategy.

Prediction of alcohol-related harm from controlled drinking strategies and alcohol consumption trajectories

Aims To establish predictors of age 21 alcohol-related harm from prior drinking patterns, current levels of alcohol consumption and use of controlled drinking strategies.

Participants One thousand, five hundred and ninety-six students recruited from an initial sample of 3300 during their final year of high school in 1993.

Design Longitudinal follow-up across five waves of data collection.

Setting Post high school in Victoria, Australia.

Measurements Self-administered surveys examining a range of health behaviours, including alcohol consumption patterns and related behaviour.

Findings Drinking behaviours at age 21 were found to be strongly predicted by drinking trajectories established through the transition from high school. Multivariate regression analysis revealed that alcohol-related harms at age 21 were reduced where current levels of alcohol use fell within limits recommended in Australian national guidelines. After controlling for this effect it was found that the range of strategies employed by participants to control alcohol use maintained a small protective influence. Post-high-school drinking trajectories continued to demonstrate a significant effect after controlling for current behaviours. Findings revealed that over one quarter of males and females drank alcohol, but on a less-than-weekly basis. This pattern of alcohol use demonstrated considerable stability through the post-school transition and was associated with a low level of subsequent harm at age 21.

Conclusions Future research should investigate whether encouraging more Australian adolescents to drink alcohol on a less-than-weekly basis may be a practical intervention target for reducing alcohol-related harms.

Mental health promotion and socio-economic disadvantage: lessons from substance abuse, violence and crime prevention and child health

Issue addressed: Mental health promotion aimed at populations with low socio-economic status (SES) may benefit by investigating prevention strategies that effectively address related child and adolescent problems.
Methods: Evidence from a number of literature reviews and program evaluations was synthesised. First, the impact of SES on development from childhood to adulthood is considered in light of research on substance
abuse, violence, crime, and child development problems. Second, evaluations of interventions are reviewed to identify those that have shown outcomes in research studies (efficacy) or in real-world settings (effectiveness) in reducing developmental problems associated with low SES. Low SES is measured in different ways including low levels of education and/or income or definitions that combine several variables into a new indicator of low SES.
Results: Factors associated with low SES are also associated to varying extent with the development of violence and crime, substance abuse and child health problems. Interventions that address underlying determinants of low SES show strong efficacy in decreasing adolescent crime and violence and effectiveness in improving child health outcomes. Although there is limited efficacy evidence that substance abuse prevention can be effectively addressed by targeting low SES, programs designed to improve educational pathways show some efficacy in reducing aspects of adolescent substance use.
Conclusion: Mental health promotion strategies can draw on the approaches outlined here that are associated with the prevention of child and adolescent problems within low SES communities. Alternatively, such interventions could be supported in mental health promotion policy as they may assist in preventing related problems that undermine mental health.

Alcohol use and related harms in school students in the USA and Australia

Recognizing there have been few methodologically rigorous cross-national studies of youth alcohol and drug behaviour, state student samples were compared in Australia and the USA. Sampling methods were matched to recruit two independent, state-representative, cross-sectional samples of students in Grades 5, 7 and 9 in Washington State, USA, (n = 2866) and Victoria, Australia (n = 2864) in 2002. Of Washington students in Grade 5 (age 11), 10.3% (95% CI 7.2–14.7) of boys and 5.2% (95% CI 3.4–7.9) of girls reported alcohol use in the past year. Prevalence rates were markedly higher in Victoria (34.2%, 95% CI 28.8–40.1 boys; 21.0%, 95% CI 17.1–25.5 girls). Relative to Washington, the students in Victoria demonstrated a two to three times increased likelihood of reporting substance use (either alcohol, tobacco or illicit drug use), and by Grade 9, experiences of loss-of-control of alcohol use, binge drinking (frequent episodes of five or more alcoholic drinks), and injuries related to alcohol were two to four times higher. The high rates of early age alcohol use in Victoria were associated with frequent, heavy and harmful alcohol use and higher overall exposure to alcohol or other drug use. These findings reveal considerable variation in international rates of both adolescent alcohol misuse and co-occurring drug use and suggest the need for cross-national research to identify policies and practices that contribute to the lower rate of adolescent alcohol and drug use observed in the USA in this study.

Association of adolescent symptoms of depression and anxiety with alcohol use disorders in young adulthood : findings from the Victorian Adolescent Health Cohort Study

Objective: To examine the association of adolescent depression and anxiety symptoms with alcohol abuse or dependence in young adulthood.

Design, setting and participants: Cohort study of the health and wellbeing of adolescents and young adults in Victoria, assessed at 8 waves (periods) of data collection, from age 14 to 24 years, between 1992 and 2003. Young people who participated in the cohort study at least once during the six adolescent assessment points (conducted 6 months apart, from age 14 to 17 years), at least once during young adulthood and who were alive at Wave 8 (n = 1758).

Main outcome measure: Alcohol abuse or dependence assessed using the alcohol and substance abuse modules of the Composite International Diagnostic Interview at age 24 years.

Results: Adolescents with moderate to high levels of depression and anxiety symptoms (measured by the revised Clinical Interview Schedule) had an increased risk of alcohol abuse or dependence in young adulthood, compared with young adults with low levels of adolescent depression and anxiety symptoms, after adjusting for potential confounding factors. Risk was higher for those with symptoms at more than two adolescent assessment points (odds ratio [OR] 1.9; 95% CI, 1.7–2.0) and for those with symptoms at one or two assessment points (OR 1.3; 95% CI, 1.2–1.4), compared with those with no above-threshold symptoms in adolescence.

Conclusions: Adolescents with depression and anxiety symptoms are at increased risk for alcohol use disorders into young adulthood. They warrant vigilance from primary care providers in relation to alcohol use well into adulthood.

Alcohol consumption, obesity, and psychological distress in farming communities — an Australian study

Purpose: Alcohol consumption patterns nationally and internationally have been identified as elevated in rural and remote populations. In the general Australian population, 20.5% of adult males and 16.9% of adult females drink at short-term, high-risk levels. Farmers are more likely to drink excessively than those living in major cities. This study seeks to explore the relationships between farmers’ physical and mental health and their alcohol consumption patterns. Our hypothesis is that farmers consume alcohol at high-risk levels more often than the Australian average and that this consumption is associated with obesity and psychological distress.

Methods: Cross-sectional descriptive data were collected within Australian farming communities from 1,792 consenting adults in 97 locations across Australia. Data on anthropometric measurements, general physical attributes and biochemical assessments were used to explore the interrelationships of self-reported alcohol consumption patterns with obesity, psychological distress, and other physical health parameters.

Findings: There was a higher prevalence of short-term, high-risk alcohol consumption (56.9% in men and 27.5% in women) reported in the study compared with national data. There was also a significant positive association between the prevalence of high-risk alcohol consumption and the prevalence of obesity and abdominal adiposity in psychologically distressed participants.

Conclusions: The prevalence of short-term, high-risk alcohol consumption practices in this cohort of farming men and women is significantly higher than the Australian average. These consumption practices are coupled with a range of other measurable health issues within the farming population, such as obesity, hypertension, psychological distress, and age.

Adolescent predictors and environmental correlates of young adult alcohol use problems

To examine the rates of young adult alcohol and drug use and alcohol problems, adolescent predictors of young adult alcohol problems and correlations with young adult social, work and recreational environments.

Alcohol use and falls among the elderly in Metropolitan São Paulo, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)